Probe Melting Technology for Rapid Detection of Drug Resistant Tuberculosis

NCT02776150 | Unknown DMC

• 1 other identifier: BeijingH
• Study Type: observational
• Target: 3,100
• Locations: 0 countries
• Sites: N/A

Brief Summary

Background: Drug resistant tuberculosis is a serious public health problem that threatens the health of human life and the development of society and economy. At present, the diagnosis of drug-resistant tuberculosis mainly depends on traditional drug susceptibility test. But it is limited in Mycobacterium tuberculosis slow growth speed, traditional solid drug sensitivity test usually need to 3 months to results, delay the development of drug resistance in patients with effective treatment. Probe melting curves resistance detection technology is the recent emergence of a new molecular biology and drug resistant tuberculosis detection technology, probe melting curves with different fluorescent labeled probe coverage detection specific to M.tuberculosis drug resistance determining region, through changes in the melting point of the probe hybridization, acquire mutation information of detection region, shorten detection time and detect nonuniform resistance. In this study, by selecting a nationally representative in different levels of hospitals jointly launched multi center, large sample clinical assessment, completed the comprehensive evaluation of sensitivity, specificity and health economics of drug resistant pulmonary tuberculosis, especially resistance to multidrug and extensively drug-resistant TB patients detection,in order to evaluate the rapid, accurate and economic and appropriate technology of drug resistance pulmonary tuberculosis detection. In order to accomplish the overall goal of the project, in the framework of the overall design, according to the principles of the core tasks are divided into four sub topics, namely: Sub topic 1 of the core mission is included in 3100 cases of smear positive pulmonary TB suspicious symptoms, from which selected more than 1000 cases of drug-resistant pulmonary tuberculosis patients, using MGIT liquid culture and drug sensitivity test as the gold standard,evaluate the sensitivity and specificity of probe melting curves in detction of resistance of four kinds of anti tuberculosis drug to Mycobacterium tuberculosis; Sub topic 2 core task is including at least 500 cases of culture positive pulmonary tuberculosis patients and treatment follow-up, using MGIT liquid culture and drug sensitivity test as the gold standard, evaluate the application value of probe melting curves for monitoring spectrum changes of drug resistance of Mycobacterium tuberculosis during pulmonary tuberculosis treatment. The core mission of sub topic 3 is to project implementation of hospital as the research site,acquire the cost-effect evaluation and analysis by comparing probe melting technology with Mycobacterium tuberculosis MGIT liquid culture, and drug sensitivity test with xpert MTB/RIF technology.

Conditions

Tuberculosis, Pulmonary

Keywords

probe melting curve; Drug resistance; Tuberculosis, Pulmonary

Outcome Measures

Primary Outcomes (4)

• the sensitivity and specificity of probe melting curves technology

  assess the sensitivity and specificity of probe melting curves for four kinds of anti tuberculosis drug resistance to Mycobacterium tuberculosis.

  up to 3.5 years

• Comparison of diagnostic efficacy

  Using Xpert-MTB/RIF as control technology, the diagnostic efficacy of two kinds of drug resistance detection technology was compared.

  from January,2015 to December,2018

• Evaluation of the application value of probe melting curve technology

  For the first time in China to carry out drug-resistant TB rapid detection technology appllied in the follow-up, improve the resistance detection technology to monitor the change of TB drug resistance spectrum in the treatment of pulmonary tuberculosis.Selecting patients with MGIT liquid culture positive pulmonary tuberculosis(selected from sub topic1) were included in the study，at least 500 patients were included in the study.Observe the outcomes and the change of drug resistance spectrum.drug-resistant TB rapid detection technology applied in the follow-up of patients with pulmonary TB by monitoring TB drug resistance spectrum change,provides the basis for the resistant phenotype and genotype identification and diagnosis of nonuniform resistance.Data statistics and analysis:95% confidence intervals, chi square test and Kappa test were calculated respectively.

  up to 3.5 years

• analyze the cost-effect assessment of probe melting curve technology and other two kinds of detection methods

  Complete the cost-effectiveness assessment analysis of the probe melting curve technology compared with Mycobacterium tuberculosis MGIT liquid culture and drug sensitivity test,and xpert MTB / RIF technology. Methods:Using cost analysis and acceptability questionnaire.Each of the implementation of the hospital, collecting the basic data and input the costs into the software,using opportunity cost method.

  up to 3.5 years

Study Arms (3)

MGIT liquid culture+drug sensitivity test

MGIT: The bactec MGIT 960 system is non-radiometric. It uses MGIT media and patented sensors, making efficient use of advanced fluorometric technology, which permits highly accurate detection of O2 consumption without sharps. Automated quality control is performed continuously to ensure precise and reliable operation. Results are provided as positive/negative and numerical growth units.

Xpert-MTB/RIF

xpert-MTB/RIF: The Xpert MTB/RIF assay is a nucleic acid amplification (NAA) test that uses a disposable cartridge with the GeneXpert Instrument System. A sputum sample is collected from the patient with suspected TB. The sputum is mixed with the reagent that is provided with the assay, and a cartridge containing this mixture is placed in the GeneXpert machine. All processing from this point on is fully automated.The test simultaneously detects Mycobacterium tuberculosis complex (MTBC) and resistance to rifampin (RIF) in less than 2 hours.

probe melting curve detection

Probe-based fluorescence melting curve analysis (FMCA) is a powerful tool for mutation detection based on melting temperature generated by thermal denaturation of the probe-target hybrid, which performed for Mycobacterium tuberculosis's drug resistant monitor. The method was explored two dual-labeled, self-quenched probes, TaqMan and shared-stem molecular beacons, in their ability to conduct FMCA. Both probes could be directly used for FMCA and readily integrated with closed-tube amplicon hybridization under asymmetric PCR conditions. Improved flexibility of FMCA by using these probes was illustrated in three representative applications of FMCA: mutation scanning, mutation identification and mutation genotyping, all of which achieved improved color-multiplexing with easy probe design and versatile probe combination and all were validated with a large number of real clinical samples.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

the population of suspected symptoms of tuberculosis with sputum smear microscopy positive

You may qualify if:

• During the study of all smear positive pulmonary tuberculosis with suspicious symptoms
• Can provide 3-4ml sputum samples three times in 2 days
• Informed consent

You may not qualify if:

• The quality of the sputum sample is not qualified (the sputum sample is less than 3ml or saliva sputum)

Sponsors & Collaborators

• Beijing Hospital: lead

Related Publications (23)

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MeSH Terms

Conditions

Tuberculosis, Pulmonary

Condition Hierarchy (Ancestors)

Tuberculosis; Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Respiratory Tract Infections; Lung Diseases; Respiratory Tract Diseases

Central Study Contacts

Yanming Li, Principal Investigator

CONTACT

13701097436; lymyl@263.net

Shuyi Si, subordinate

CONTACT

13051991568; shy_si@163.com

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: chief physician

Study Record Dates

• First Submitted: May 10, 2016
• First Posted: May 18, 2016
• Study Start: May 1, 2016
• Primary Completion: December 1, 2018
• Study Completion: June 1, 2019
• Last Updated: May 18, 2016

Record last verified: 2016-05

Data Sharing

• IPD Sharing: Will share